The goal of this proposal is to investigate the role of ICER in ovarian function. ICER functions as a transcriptional repressor and is a product of the cAMP Responsive Element Modulator (CREM) gene. The main focus of research in Dr. Molina's lab has been in providing evidence in supporting the hypothesis that ICER acts as a tumor suppressor gene product. ICER can be detected in normal cells, but is undetectable in such tumors cells like prostate tumor cells and human ovarian granulosa tumor cells. ICER is highly expressed in human ovarian tissue and its expression is induced by LH in the ovaries of immature rats. Conversely, LH reduces cyclin D2 expression and its levels are low in the rat's corpus luteum. Additionally, our lab has shown that ICER blocks PKA-induced DNA synthesis and represses the activity of cyclin D2 promoter in cultured granulosa cells. Our hypothesis is that ICER regulates ovarian granulosa cell growth and differentiation by controlling the expression of cyclin D2. This hypothesis will be tested using a transgenic mouse model in which the permissible (Tet-On) expression of ICER is restricted to ovarian granulosa cells and regulated by FSH.